Tumor metastasis is the dominant cause of death in cancer patients, including oral tongue squamous cell carcinoma (SCC) patients. The presence of lymph node metastasis in the neck is an important prognostic factor and crucial in making clinical decisions regarding postoperative treatments and follow ups. However, the current clinical diagnosis of lymph node metastasis for early stage (T1-T2) oral tongue cancer is not ideal. Occult nodal metastasis can be expected in over 30% of patients with T1 and T2 tongue cancers and clinically metastasis negative (N0) necks. It is critically important to identify those cancers with metastasis potential for more aggressive therapy. The identification of molecular markers associated with the metastasis and the development of a prediction model based on these markers will improve clinical treatment decisions in the management of this dreadful cancer and would help to facilitate the development of therapeutic interventions for oral tongue SCC patients. This proposal aims to test the hypothesis that signature genomic and expressional alternations exist in oral tongue cancer that distinguish tumors that metastasize from those that do not. Patient resources are in place to permit genomic and expressional studies including early stage (T1-T2) oral tongue cancer patients with known metastasis outcome (Aim 1). Bioinformatics and biocomputational expertise are in place to harness diagnostic molecular determinants in the metastatic oral tongue cancers and to build molecular classification model for tongue cancer metastasis (CMTCM) (Aim 2). Aim 3 is to test the classification models in a multi-center setting to evaluate the clinical utility of this classification/prediction models for oral tongue cancer metastasis. The overarching aim of the proposal is to translate genome-wide discoveries into a predictive model that can forecast metastatic potential of early stage oral tongue SCC, and thus improve clinical treatment decisions in the management of oral tongue cancer. Relevance to Public Health (Project Narrative): This research project will lead to the discovery of biomarkers that can be used for the detection of oral tongue cancer metastasis, which will improve the management and treatment of oral tongue cancer patients.